The long-term objective is to develop a new approach to treat cardiac arrest. Currently, despite early, successful defibrillation in half the patients, the overall mortality rate is 95%. Furthermore, approximately 70% of these few survivors of whole body ischemia develop neurologic injury: we may save the heart, but lose the brain. The causative factors are inadequate treatment of the underlying cause of arrest by insufficient a) delivery of brain flow during CPR, b) restoring of heart blood supply to allow it to recover, and c) correction of the underlying cardiac cause. A novel approach will be taken to 1) promptly use the heart lung machine without opening the chest by an approach through leg vessels to mechanically, and temporarily, take over heart function, 2) change its prime pharmacologically to make a metabolic fuel for recovery, and 3) correct the underlying cause. We will use a relevant surgical model of either deep hypothermic circulatory arrest (DHCA) or lethal normothermic ventricular fibrillation for 10 minutes to cause whole body ischemia. Both insults cause high mortality and brain damage. We will present pilot studies showing complete heart and 100% brain recovery by integrating the specific aims of these three interventions. These results were achieved by use of a standard prime of the CPB circuit, and adding either a sodium hydrogen exchange inhibitor or specially filtering the white blood cells that cause reperfusion damage. We will extend the period of ischemia to two hours and show how this cardiac arrest model (that permits regional brain flow through the carotid arteries) can also be used to treat stroke. If this novel method of management is correct, the scheme of diagnosis and management of this almost always fatal cardiac arrest complex will change markedly.